Sweatman: Rx of Renal Cancer

Question 1

What is the best curative treatment in renal cancer?

Answer 1

surgical excision

Question 2

What are common sites of metastatic growth in renal tumors?

Answer 2

lymph nodes (most common)
lung, liver, bone (destructive lesions)
adrenal gland
brain
opposite kidney
subcutaneous skin nodules

Question 3

What is the most common renal tumor in children called?

Answer 3

Nephroblastoma (Wilm’s Tumor)

Question 4

T or F: WIlm’s tumor is highly curable

Answer 4

T. 5 year survival rate is consistently above 90%

Question 5

Standard chemotherapy postnephrectomy in pts with Wilm’s tumor involves 3 different regimen options. Each one has what drug in common?

Answer 5

Vincristine

1. Vincristine + dactinomycin (18 weeks)
2. Vincristine + dactinomycin + doxorubicin (24 weeks)
3. Vincristine + doxorubicin +cyclophosphamide + etopside (24 weeks)

Question 6

Treatment for recurrent disease in Wilm’s tumor patients involves alternating courses of what two tx regimens?

Answer 6

1. Vincristine, doxorubicin, cyclophosphamide

2. etopside and cyclophosphamide

Question 7

T or F: treatment of clear cell sarcoma is similar to the treatment of nephroblastoma (wilm’s tumor)

Answer 7

T. treatment options involves 2 standard regimens used in the treatment of Wilm’s tumor PLUS RADIATION THERAPY

Question 8

Patients with recurrent clear cell sarcoma involving the brain have benefited from what tx?

Answer 8

ICE (ifosfamide, carboplatin, etopside) coupled with local control (surgical resection and/or radiation)

Question 9

In the tx of childhood tumors, all of the drugs have a similar ROA…?

Answer 9

IV

Question 10

Carboplatin toxicities

Answer 10

infection susceptibility

Question 11

cyclophosphamide and ifosfamide toxicities

Answer 11

hemorrhagic cystitis

Question 12

what can you use to treat the toxicity of cyclophosphamide and ifosfamide?

Answer 12

MESNA to treat hemorrhagic cystitis

Question 13

doxorubicin toxicities

Answer 13

acute and chronic cardiotoxicity

Question 14

dactinomycin toxicities

Answer 14

hepatic dysfunction

infection susceptibility

Question 15

etopside toxicities

Answer 15

hematologic toxicity

BP instability

Question 16

vincristine toxicities

Answer 16

bilateral sensory “stocking-glove” pattern

Question 17

What are examples of rapamycins?

Answer 17

temsirolimus

everolimus

Question 18

What is the MOA of rapamycins? net effects?

Answer 18

bind to FKBP12 and inhibit mTORC1

this inhibits cell cycle progression and angiogenesis and promotes apoptosis

Question 19

In terms of ROA and dosing regimen, how do temsirolimus and everolimus differ?

Answer 19

temsirolimus: IV weekly
everolimus: oral daily

Question 20

What metabolizes both temsirolimus and everolimus? how is temsirolimus somewhat different?

Answer 20

CYP3A4

temsirolimus is metabolized to sirolimus, likely a more important agent

Question 21

What are prominent side effects of temsirolimus and everolimus?

Answer 21

maculopapular rash
mucositis
anemia
fatigue

Question 22

What are less frequent side effect of temsirolimus and everolimus seen with progressive drug cycles?

Answer 22

reversible leukopenia

thrombocytopenia

Question 23

How can temsirolimus and everolimus affect the pulmonary system? Tx for this?

Answer 23

pulmonary infiltrates
can lead to cough, SOB

stop drug (duh)
prednisone

Question 24

What are the TKIs used in the tx of adult renal tumors?

Answer 24

sunitinib
sorafenib
pazopanib

Question 25

What do all 3 TKIs inhibit?

Answer 25

VEGF-receptor 2 and other tyrosine kinases there is a long list of other tyr kinases for each drug. you should probably look at them.

Question 26

ROA for the 3 TKIs? Metabolism?

Answer 26

oral | CYP3A4

Question 27

Response to which TKI is better (31%) and longer lasting than for other antiangiogenic drugs?

Answer 27

sunitinib

Question 28

What are common vascular toxicities observed with antiangiogenic drugs (i.e. TKIs)?

Answer 28

bleeding HTN arterial thrombotic events

Question 29

What are specific side effects of sunitinib?

Answer 29

fatigue hypothyroidism CHF (often with HTN) hand foot syndrome

Question 30

What is the BBW for pazopanib? What does this call for?

Answer 30

hepatic disease: severe and fatal hepatotoxicity has been reported liver function tests before tx, at least once weekly during first 4 months of tx, and periodically after

Question 31

What are some other side effects of pazopanib?

Answer 31

hyperbilirubinemia, especially in Gilbert's syndrome which involves glucuronidation deficiency and reduced excretion of bilirubin)??

Question 32

T or F: interferon-alpha alone is more effective in tx of metastatic renal cell carcinoma when compared to inf-alpha + bevacizumab

Answer 32

F. adding bevacizumab to interferon alfa results in significant imporvement in progression-free survival, when comapred to inf-alfa alone

Question 33

what is the MOA of bevacizumab?

Answer 33

VEGF inhibitor

Question 34

What are the main safety concerns associated with bevacizumab?

Answer 34

``` HTN arterial thromboembolic events (stroke, angina, MI) wound healing complications GI perforations proteinuria ```

Question 35

What is aldesleukin?

Answer 35

recombinant IL-2

Question 36

Aldesleukin was designated as a ____ drug for renal cell carcinoma

Answer 36

orphan (an orphan drug is one that was developed specifically to tx a rare condition. often pharmaceutical companies are given incentives to develop orphan drugs)

Question 37

What is the MOA of aldesleukin?

Answer 37

- binds IL-2 receptor on cells of the immune system - stimulates a cytokine cascade - may stimulate cytotoxic lymphocytes

Question 38

How does T sweat describe aldesleukin?

Answer 38

"VERY nasty stuff!"

Question 39

There are over 120 adverse events listed for aldesleukin. Name them all. actually, just name the 2 T sweat listed.

Answer 39

1. capillary leak syndrome-->loss of vascular tone (THIS IS RESPONSIBLE FOR MANY OF THE ADVERSE EFFECTS) 2. decreased mean arterial pression (MAP)-->decreased organ perfusion

Question 40

What is the MOA of interferon-alpha?

Answer 40

direct antiproliferative effect on the tumor cell by 1. enhance or inhibit protein synthesis 2. modify cell surface antigen expression 3. modulate immune system

Question 41

What are the net effects of interferon-alpha?

Answer 41

immunomodulatory effects: it induces a host response to the tumor which slows the rate of cell proliferation

Question 42

What are some side effects of interferon alpha?

Answer 42

``` neuropsychiatric: suicide homicidal and suicidal ideation depression relapse of drug addiction aggressive behavior ```

Question 43

T or F: interferon alfa provides a modest survival benefit compared to other commonly used treatments and should be considered for the control arm of future studies of systemic agents

Answer 43

Fact (so, true, not false)